Tumor cell procoagulant and urokinase expression in carcinoma of the ovary.
Tumor cell procoagulant and urokinase expression in carcinoma of the ovary.
复制标题
卵巢癌中肿瘤细胞促凝剂和尿激酶的表达。
DOI：
10.1093/jnci/85.15.1225
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Kudryk,BJ
中科院分区：
文献类型：
--
作者：
Zacharski,LR;Memoli,VA;Ornstein,DL;Rousseau,SM;Kisiel,W;Kudryk,BJ
背景：多年来人们一直观察到癌症和血液凝固增加之间的联系。通常，凝血系统（纤维蛋白沉积）和纤溶系统（纤维蛋白被酶降解）之间存在平衡。然而，在恶性疾病如卵巢癌中，这种平衡被破坏，导致凝血或高凝性异常激活。此外，有证据表明，这些途径的不同组成部分可能导致恶性肿瘤的无序特征，如增殖、侵袭和转移。目的：我们的目的是确定卵巢癌肿瘤细胞与凝血（促凝剂启动）和纤维蛋白溶解（尿激酶型纤溶酶原激活物启动）（u-PA）途径的相互作用模式。方法：对15例囊性上皮性卵巢癌原发肿瘤新鲜切除标本制备的丙酮-甲基苯甲酸-二甲苯固定组织进行研究。这些患者之前都没有接受过治疗。抗体在对照组织和肿瘤组织中进行测试，其浓度提供最小背景染色的最大染色强度。实验室免疫组织化学技术使用纯化的单特异性抗体来检测凝血抗原。利用重组人组织因子抗体进行试验；第七因子;X因素;XIIIA因素;u-PA的高分子量和低分子量形态；组织型纤溶酶原激活剂；纤溶酶原,物还有纤溶酶原激活物抑制剂1 2 3。用于特异性抗原检测的单克隆抗体包括1-8C6（纤维蛋白原）、T2G1（纤维蛋白）和EBM-11（巨噬细胞特异性）。结果：卵巢肿瘤细胞表达尿激酶型纤溶酶原激活物的强度和分布不同。肿瘤细胞纤溶酶原未检出。肿瘤细胞也表达组织因子和凝血途径中间体，这些组织因子和凝血途径中间体适合局部凝血酶的生成，纤维蛋白原（存在于肿瘤结缔组织中）转化为纤维蛋白，发现纤维蛋白附着在肿瘤结节和单个肿瘤细胞的表面。检测到的纤维蛋白不能根据坏死或局部炎症细胞浸润来解释。结论：这些结果与肿瘤细胞相关的促凝途径的存在一致，该途径可导致卵巢癌凝血酶生成和高凝性。意义：在卵巢癌中，促凝途径可能促进肿瘤进展。临床试验表明，一种能够限制局部凝血能力的治疗药物（抗凝剂、蛋白酶抑制剂）适用于这种肿瘤类型。[J]中华医学杂志，2004,27(2):357 - 357。
Background: An association between cancer and increased blood coagula-tion has been observed for many years. Generally, there is an equilibrium between the coagulation system (fibrin deposition) and the fibrinolytic system (degradation of fibrin by enzymes). However, in malignant disease such as ovarian carcinoma, this equilibrium is dis-rupted, resulting in the abnormal activation of coagulation or hyper-coagulability. Also, evidence indicates that various components of these pathways may contribute to the dis-orderly characteristics of malig-nancy, such as proliferation, inva-sion, and metastasis.Purpose: Our purpose was to define the mode of interaction of tumor cells in ovarian carcinoma with both the coagulation (procoagulant-initiated) and fibrino-lysis (urokinase-type plasminogen activator-initiated) (u-PA) pathways. Methods: Studies were performed on acetone-methylbenzoate-xylene-fixed tissue prepared from fresh resected primary tumor specimens from 15 patients with cystic epithelial ovarian carcinoma. None of the patients had received prior treatment. Antibodies were tested on control and tumor tissues in concentrations that provided maximum staining intensity with minimum background staining. Laboratory immunohistochemical techniques used purified, mono-specific antibodies to detect coag-ulant antigens. Tests were performed utilizing antibodies to recombinant human tissue factor; factor VII; factor X; factor XIIIA; high-molecular-weight and low-molecular-weight forms of u-PA; tissue-type plasminogen activator; plasminogen; and the plasminogen activator inhibitors 1, 2, and 3. Monoclonal antibodies used for specific antigen dectection included 1–8C6 (fibrinogen), T2G1 (fibrin), and EBM-11 (macrofphage-specific).Results: The ovarian rtumor cells expressed urokinase-typeplasminogen activator in a pattern that was variable in intensity and distribution. Tumor cell plasminogen was not detected. Tumor cells also expressed tissue factor and coagulation pathway intermediates that re- c suited in local thrombin generation as evidenced by the conversion of fibrinogen (present in tumor connecs tive tissue) to fibrin that was found to hug the surfaces of tumor nodules and individual tumor cells. Detected fibrin could not be accounted for on the basis of necrosis or a local ainflammatory cell infiltrate. Conclu- (sions: These results are consistent with the existence of a dominant tumor cell-associated procoagulant pathway that leads to thrombin gen- aeration and hypercoagulability in carcinoma of the ovary. Implications: In ovarian carcinoma the pro- acoagulant pathway may contribute to tumor progression. Clinical trials of a therapeutic drugs capable of limitinglocal coagulability (anticoagulants, protease inhibitors) are indicated in this tumor type. [J Natl Cancer Inst 85: 1225–1230, 1993]